SUMMARIES

I. BRAIN DAMAGE AT BIRTH

1 - Asphyxia at Birth
Experiments with monkeys on asphyxia at birth were undertaken in the 1950s to investigate ways to prevent cerebral palsy. The outcome was not cerebral palsy, and damage to the brain was confined to the brainstem. The inferior colliculus in the midbrain auditory pathway was always most severely involved. The inferior colliculus had been found in earlier experiments on cerebral circulation to have the highest rate of blood flow in the brain.

2 - Hypoxic Birth
In the initial experiments asphyxia was inflicted by covering the newborn monkey's head and clamping the umbilical cord, producing a sudden catastrophic cutoff of respiratory gas exchange. Cerebral palsy was found in later experiments to result from partial blocking of umbilical blood flow late in gestation. Circulatory insufficiency induced in this way led to widespread damage throughout the brain. Hypoxia is a state of partial oxygen insufficiency. Asphyxia occurs when oxygen delivery is completely blocked and if not fatal results in a predictable pattern of brainstem damage.

3 - Asphyxia Versus Hypoxia
Asphyxia is different from hypoxia. Protective mechanisms go into effect to preserve oxygen delivery to the inferior colliculus during a period of hypoxia. High blood flow to the inferior colliculus supports a high rate of aerobic metabolism, generating high levels of carbon dioxide. Hemoglobin delivers oxygen in exchange for carbon dioxide, an immediate adjustment that ensures continuing support of aerobic metabolism in this nucleus of the auditory system. The rest of the brain then becomes deprived of oxygen, and over time widespread damage occurs.

4 - Human Conditions
Asphyxia causes a sudden and catastrophic cessation of aerobic metabolism that is often fatal. Damage to the inferior colliculus is evident in children and adults who survive for at least several days following resuscitation. In the 1960s damage involving only the brainstem was thought to underlie what was then referred to as "minimal cerebral dysfunction."

5 - Stages of Asphyxia
Monitoring what happens during the stages of asphyxia indicates that the heart, brain, and other organs incur compromise earlier than the time required for visible damage to be evident.

6 - The Umbilical Cord Lifeline
Clamping of the umbilical cord at birth is a human invention and a dangerous procedure if performed on an infant who is not yet breathing. Respiration is the most immediate and essential need of all life forms dependent upon oxygen. Placental respiration must be maintained until an infant's lungs and heart have completed the transition from pre- to postnatal adaptation.

7 - Developmental Delay
Monkeys subjected to asphyxia at birth exhibited muscle weakness and delay in developing motor control; they never overcame poor manual dexterity. The asphyxiated monkeys were not deaf, despite the conspicuous damage to the inferior colliculus, but they did not orient to sounds as normal monkeys did.

8 - Poor Manual Dexterity
Monkeys subjected to asphyxia at birth remained deficient in manual dexterity. Large and laboriously produced handwriting is characteristic of children with developmental delay and children with "high functioning" autism.

9 - Progressive Degeneration
Widespread degeneration was evident in the brains of monkeys who survived several months or years following asphyxia at birth. Anomalies of the same brain areas (cerebellum, amygdala, corpus callosum, etc.) are evident in the brains of individuals who were autistic in childhood.

10 - Autism and Complications at Birth
Many children with autism suffered complications at birth. Oxygen insufficiency is the greatest danger during a difficult birth. Problems during labor and delivery are frequently attributed to pre-existing genetic factors, but monkeys subjected to experimental asphyxia had no pre-existing problems.

11 - Mercury, and Other Toxic Factors
In the experiments with monkeys the effects of high levels of bilirubin (jaundice) were investigated. Bilirubin did not enter brain tissue except in monkeys that had been subjected to asphyxia. Mercury preservatives in vaccines and other substances may also only cross a blood-brain barrier compromised by asphyxia or hypoxia. Does the hepatitis-B vaccine need to be given in the newborn nursery?
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II. THE AUDITORY SYSTEM

12 - Metabolic Rank Order
Methods to measure cerebral circulation were extended to measure aerobic metabolism. The same brainstem nuclei with highest blood flow were found by several measures to have highest aerobic metabolism. The inferior colliculus is at the top of the rank order by every measure.

13 - The Auditory System
The inferior colliculus evolved to provide auditory alerting for visual attention. The auditory system is always active, even during sleep. The auditory and visual colliculi of the midbrain tectum may be the locus of consciousness in the brain.

14 - Auditory Dysfunction
Children with autism are often over-sensitive to loud sounds and noisy environments (hyperacusis). Auditory evoked potential testing indicates delay of signal transmission in some children with autism. Auditory dysfunction raises the possibility of auditory system impairment by asphyxia at birth. Asphyxia of duration too brief to produce visible damage may still lead to impairment of neurotransmitter systems in the inferior colliculus.

III. LANGUAGE

15 - Language by Ear
Most children learn language by ear. Language learning begins before the language circuits of the temporal and frontal lobes are fully myelinated and mature. Children normally learn language through recognition of stressed syllables, which leads to the well recognized stage of language development known as "telegraphic speech" (baby talk).

16 - Verbal Auditory Agnosia
"Agnosia" is a failure of recognition in the apparent absence of sensory deficit. Agnosia for speech sounds has been reported in some children with autism, and has been termed "verbal auditory agnosia." At least three cases of verbal auditory agnosia have been reported in adults following damage of the inferior colliculus.

17 - Echolalic Speech
Some children with autism begin to use parroted phrase fragments (echolalic speech) at the time most children are at the "telegraphic speech" stage of development. The child who hears syllable boundaries is able to detect small units of meaning (morphemic units), to recognize their recurrence in the speech of those around him, and eventually to rearrange their use in new contexts. Use of phrase fragments indicates failure to detect syllable boundaries, and again raises the issue of auditory dysfunction in autism.

18 - Echolalic Speech is Pragmatic
Kanner (in 1946) referred to the echolalic speech of autistic children as "irrelevant and metaphorical speech." The irrelevant nature of echolalic speech is because of its use out of context; its partial fit to context makes it seem metaphorical. Phrase fragments are not as easily rearranged as morphemic units to fit context. "You don't want to go swimming?" was not a question, but one autistic child's emphatic statement that she didn't want to go in the water; this statement also provides an example of "pronoun reversal."
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IV. CHILDHOOD HANDICAPS

19 - Auditory and Motor Handicaps
Motor handicaps associated with the brainstem pattern of damage were transient and overcome except for manual dexterity in monkeys subjected to asphyxia at birth. More serious permanent disorders of movement indicate impairment of function in the basal ganglia or cerebral cortex. Most children with autism show signs of both, thus signs of damage caused by both asphyxia and hypoxia. Asphyxia is more likely to occur as the final insult of a difficult hypoxic birth. Signs of auditory dysfunction in children with autism would seem to indicate catastrophic impairment of aerobic metabolism by asphyxia at birth or by any of the other medical conditions associated with autism.

20 - Increased Incidence of Autism
The increased prevalence of autism is more likely due to increased incidence of asphyxia at birth than to increases in the medical conditions associated with autism. Textbooks on obstetrics in the late nineteenth and early twentieth centuries stressed the importance of leaving the umbilical cord intact until the newborn infant is breathing. The modern procedure of immediate umbilical cord clamping needs to be investigated as a possible cause of increased prevalence of auditory dysfunction in children.

21 - Fetal to Postnatal Adaptation
The alveoli of the lungs become functional by perfusion with blood at birth. Resuscitation by ventilation in the intensive care unit often requires use of blood volume expanders. Normal blood volume is best ensured by maintaining placental circulation through the umbilical cord.

22 - Forgotten History
Experimental asphyxiation of newborn monkeys would no longer be permissible. But the findings of past research projects remain important and merit re-examination.

23 - Worth Remembering
Comments made by Windle in 1969 are worth heeding still today, especially:
(a) To clamp the umbilical cord immediately is equivalent to subjecting the infant to a massive hemorrhage.
(b) It is no longer acceptable to assume that the human infant will escape harm from a short exposure to asphyxia at birth.
(c) Although improvement can be expected, we know that the brain of a "recovered" monkey is damaged whereas we only assume that the brain of a "recovered" human infant is normal.

24 - Hemoglobin
The release of oxygen from hemoglobin provides an explanation for why the effects of hypoxia are so different from those of asphyxia. The quickest adjustment to an environment of oxygen insufficiency is provided by the action of hemoglobin in delivering oxygen first to tissues producing the most carbon dioxide. The inferior colliculus is spared under hypoxic conditions, but first to sustain damage during any catastrophic interference with aerobic metabolism

25 - Postnatal Anemia
Clamping the umbilical cord at birth is equivalent to subjecting the infant to a massive hemorrhage; this loss of blood was shown over 60 years ago to lead to anemia in infancy. An anemic child is in a state of chronic hypoxia, which will impede normal growth of brain and other organs.

26 - Autism in Twins
Concordance of autism in identical twins is not 100 percent. Differences between concordant twin pairs are greater than similarities. Twins are more vulnerable to perinatal problems, which is also evident from the larger than would be expected number of non-identical twin pairs in which both are autistic.

27 - Male-Female Differences
Males have higher metabolic needs than females and are thus more vulnerable to any factor that interferes with aerobic energy production. Males outnumber females in most developmental disorders. Growth retardation was immediately evident in males but not females following neonatal asphyxia in laboratory rats.
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V. BRAINSTEM DAMAGE

28 - Variable Vulnerability
Protective mechanisms increase blood flow to the inferior colliculus in any circumstance that leads to impairment of aerobic metabolism. This has been revealed in several experiments with toxic chemicals. Total catastrophic disruption of aerobic metabolism damages the rank order of brainstem nuclei of high metabolic rate. Partial interference with aerobic metabolism spares the inferior colliculus and leads to damage of less metabolically active brain centers.

29 - Patterns of Damage
Circulatory insufficiency most often leads to damage of the cerebral cortex. Brainstem damage with or without involvement of cortical areas has been reported in people resuscitated after drowning, suffocation, or cardiac arrest. Brainstem damage has often been compared with that found in monkeys asphyxiated at birth and also in Wernicke's encephalopathy.

30 - Wernicke's Encephalopathy
Gayet (in 1875) and Wernicke (in 1881) described damage restricted to the brainstem in cases of airway damage, alcoholism, and ingestion of sulfuric acid. This pattern of damage is associated most often with alcoholism and thiamine (vitamin B1) deficiency.

31 - Suffocation at the Molecular Level
An increasing array of toxic substances has been found to interfere partially or catastrophically with aerobic metabolism. Brainstem nuclei are affected in varying degrees.

32 - Thiamine Deficiency
Thiamine (vitamin B1) is an essential cofactor for enzymes of aerobic metabolism. Deficiency of thiamine in the diet or because of malabsorption in gastrointestinal disorders leads to Wernicke's encephalopathy or variants of this pattern of damage.

33 - Brain-Gut Relationship
Autonomic functions such as intestinal peristalsis are controlled by brainstem centers. Damage to these autonomic centers can impair intestinal function. Intestinal dysfunction in turn leads to malabsorption and/or absorption of digestional fragments that should be excluded. Toxic fragments of digestion may be toxic to the brain and further compound the effects of earlier damage.